The overall aim of this grant proposal is to understand the interaction of T cells and retrovirus-encoded superantigens. Superantigens have been implicated in the pathogenesis of certain infectious diseases in both mouse and man. They may also play a role in certain autoimmune diseases. Experiments in Specific Aim A. are designed to determine how mouse mammary tumor virus (MMTV)-encoded superantigens interact with. major histocompatibility complex (MHC) class II and T cell receptor (TCR) molecules. This application seeks to perform site-directed mutagenesis and transfection of MMTV-encoded superantigens to determine important amino acids contributing to their interaction with MHC and TCR. In addition, to understand better the structure of MMTV-encoded superantigens, over-production of soluble MMTV-encoded superantigens, which will be used for X-ray crystallographic studies, are proposed (Aim B.). Experiments are designed to produce soluble MMTV-superantigens in bacteria and/or mammalian cells. Finally, experiments in Specific Aim C. are proposed to identify and characterize the molecules involved in T cell proliferation by human T-cell leukemia virus type-I (HTLV-I). The experiments will involve the analysis of TCR usage in T cell proliferation by HTLV-I and the transfection of HTLV-I genes in order to determine whether HTLV-I-induced T cell proliferation is mediated by superantigens and what the superantigen structure might be. The knowledge gained from studies in this application will provide important insight into the pathogenesis of certain retrovirus-induced diseases, and may provide a basis for the design of new therapeutic strategies.